Combining for a Cure

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Working with Jaffee, Laheru, Lei Zheng and Ella-Mae Shupe, Lee’s focus is on locally advanced pancreatic cancer. Although the cancer has not invaded other organs (metastatic), it has begun to attach itself to the tissue and vessels around the pancreas and, as a result, it cannot be treated with surgery. About 40 percent of patients diagnosed have this form of the cancer. “Right now, we don’t have many treatment options for them,” says Lee. They receive the same treatment that patients with metastatic pancreatic cancer get, she says.

Lee’s approach could make curative surgery an option for many more patients. It combines anticancer drugs, a pancreatic cancer vaccine, an exciting new type of immune therapy known as an immune checkpoint blockade and a very precise form of radiation therapy called stereotactic body radiation therapy.

The therapy uses standard anticancer drugs to stabilize the cancer, followed by the Jaffee-developed pancreatic cancer vaccine. The vaccine awakens the immune system, summoning cancer-fighting killer T cells to the tumor. Treatment with a new checkpoint blockade immune therapy known as anti-PD-1 disrupts a mechanism cancer cells use to hide from these T cells. Lee hopes that together, these therapies will cause the patient’s own immune system to attack the cancer. Patients receive two doses of this combined regimen three weeks apart.

Next, patients begin five days of radiation therapy. This treatment destroys pancreatic cancer cells and also awakens the immune system, Lee says. As cancer cells die, they release their proteins into the body. Essentially, they show their true colors to the immune system, which now recognizes them as abnormal cells; immune cells are then deployed to the tumor. Patients will then, hopefully, get surgery and chemotherapy, followed by more immunotherapy, with the goal of keeping the tumors at bay.

With funding support from the United Company Charitable Foundation and the James W. and Frances Gibson McGlothlin Foundation of Bristol, Va, the Kimmel Cancer Center will soon begin a clinical trial in 54 patients to study the combined therapy. Lee wants to see if it works well enough against the cancer to get more patients to surgery, where their cancers could be cured. At a minimum, she hopes it will keep patients’ cancers from spreading- and potentially keep them in check for a long time.